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Abstract Preventive treatments for unruptured intracranial aneurysms (UIAs) are used worldwide. However, the long-term effects to cognition have been underestimated. Using representative sample data from the National Health Insurance Service-Senior Cohort database, we compared cumulative risk of incident dementia between two groups: (1) treatment versus observation group, and (2) within the treatment group (surgical versus endovascular treatment). Cox proportional hazard ratios were estimated after applying one-to-one propensity score matching. Subgroup analyses were conducted to investigate interactions between treatment effects and sex, age and history of stroke, respectively. After matching, 3,763 participants were included in each group. The 10-year incidence rates of dementia were 9.82 and 8.68 per 1,000 person-years in the treatment and observation groups, respectively (HR: 1.11, 95% CI: 0.90–1.38, P = 0.33). Furthermore, the risk of incident dementia was not different between the surgical and endovascular treatment groups (HR: 0.98, 95% CI: 0.70–1.37, P = 0.91). In the subgroup analysis, surgical treatment was associated with an increased risk of developing dementia, particularly among male patient (HR: 2.34, 95% CI: 1.04–5.28). Preventive treatment of UIAs appears acceptable in terms of long-term effects to cognition. However, further researches are strongly required to identify the high risk patients of development of dementia.

Abstract Background Determining the impact of somatic mutations requires understanding the functional relationship of genes acquiring mutations; however, it is largely unknown how mutations in functionally related genes influence each other. Methods We employed non-synonymous-to-synonymous or dNdS ratios to evaluate the evolutionary dependency (ED) of gene pairs, assuming a mutation in one gene of a gene pair can affect the evolutionary fitness of mutations in its partner genes as mutation context. We employed PanCancer- and tumor type-specific mutational profiles to infer the ED of gene pairs and evaluated their biological relevance with respect to gene dependency and drug sensitivity. Results We propose that dNdS ratios of gene pairs and their derived cdNS (context-dependent dNdS) scores as measure of ED distinguishing gene pairs either as synergistic (SYN) or antagonistic (ANT). Mutation contexts can induce substantial changes in the evolutionary fitness of mutations in the paired genes, e.g., IDH1 and IDH2 mutation contexts lead to substantial increase and decrease of dNdS ratios of ATRX indels and IDH1 missense mutations corresponding to SYN and ANT relationship with positive and negative cdNS scores, respectively. The impact of gene silencing or knock-outs on cell viability (genetic dependencies) often depends on ED, suggesting that ED can guide the selection of candidates for synthetic lethality such as TCF7L2-KRAS mutations. Using cell line-based drug sensitivity data, the effects of targeted agents on cell lines are often associated with mutations of genes exhibiting ED with the target genes, informing drug sensitizing or resistant mutations for targeted inhibitors, e.g., PRSS1 and CTCF mutations as resistant mutations to EGFR and BRAF inhibitors for lung adenocarcinomas and melanomas, respectively. Conclusions We propose that the ED of gene pairs evaluated by dNdS ratios can advance our understanding of the functional relationship of genes with potential biological and clinical implications.

Key Clinical Message In previous reports, hypothyroidism, hypopituitrism, and hypogonadism were common endocrine causes of SCFE, but this is the first time that congenital adrenal hyperplasia has been observed. As such, patients who have undergone long‐term endocrine treatment for congenital adrenal hyperplasia could potentially be subjected to a higher risk for SCFE.

Objectives: Adjusting for potential confounders is crucial for producing valuable evidence in outcome studies. Although numerous studies have been published using the Korea National Health Insurance Claim Database, no study has critically reviewed the methods used to adjust for confounders. This study aimed to review these studies and suggest methods and applications to adjust for confounders. Methods: We conducted a literature search of electronic databases, including PubMed and Embase, from January 1, 2021 to December 31, 2022. In total, 278 studies were retrieved. Eligibility criteria were published in English and outcome studies. A literature search and article screening were independently performed by 2 authors and finally, 173 of 278 studies were included. Results: Thirty-nine studies used matching at the study design stage, and 171 adjusted for confounders using regression analysis or propensity scores at the analysis stage. Of these, 125 conducted regression analyses based on the study questions. Propensity score matching was the most common method involving propensity scores. A total of 171 studies included age and/or sex as confounders. Comorbidities and healthcare utilization, including medications and procedures, were used as confounders in 146 and 82 studies, respectively. Conclusions: This is the first review to address the methods and applications used to adjust for confounders in recently published studies. Our results indicate that all studies adjusted for confounders with appropriate study designs and statistical methodologies; however, a thorough understanding and careful application of confounding variables are required to avoid erroneous results.

Abstract In the view of the situation where great economic loss often occurs during mining deep coal seams in Feicheng coal field due to water inrush from the floor Ordovician limestone aquifer, the floor "lower four-zone" theory was used as a guide. 81006 working face of Caozhuang Coalmine in Feicheng coal field was taken as the research background, and paste filling technology was proposed to inhibit or reduce the damaged floor depth caused by mine ground pressure in order to prevent water inrush from the floor Ordovician limestone aquifer. Glue material, coal gangue powder, and fly ash were selected as filling material, and a ground filling system, including a material production system, storage material system, power supply and water supply system, automatic control and measurement system, monitoring and control communications system, emergency response system, and underground filling system, including pipe conveyor system and working face blocking grout loss system, were established to achieve effective filling goaf. Field stress monitoring and floor damaged depth measurement showed that when reaching a steady state after a period of time, paste filling working face not only restored to the original stress state but also significantly reduced the floor's damaged depth caused by mine ground pressure. This verifies that working face with paste-like backfill technology is a very effective measure to prevent water-inrush from the floor.

Abstract Transcriptional changes in compensatory erythropoiesis in sickle cell anemia (SCA) and their disease modulation are unclear. We detected 1226 differentially expressed genes in hemoglobin SS reticulocytes compared to non-anemic hemoglobin AA controls. Assessing developmental expression changes in hemoglobin AA erythroblasts for these genes suggests heightened terminal differentiation in early erythroblasts in SCA that diminishes toward the polychromatic to orthochromatic stage transition. Comparison of reticulocyte gene expression changes in SCA with that in Chuvash erythrocytosis, a non-anemic disorder of increased erythropoiesis due to constitutive activation of hypoxia inducible factors, identified 453 SCA-specific changes attributable to compensatory erythropoiesis. Peripheral blood mononuclear cells (PBMCs) in SCA contain elevated proportions of erythroid progenitors due to heightened erythropoiesis. Deconvolution analysis in PBMCs from 131 SCA patients detected 54 genes whose erythroid expression correlated with erythropoiesis efficiency, which were enriched with SCA-specific changes (OR = 2.9, P = 0.00063) and annotation keyword “ubiquitin-dependent protein catabolic process”, “protein ubiquitination”, and “protein polyubiquitination” (OR = 4.2, P = 7.5 × 10–5). An erythroid expression quantitative trait locus of one of these genes, LNX2 encoding an E3 ubiquitin ligase, associated with severe pain episodes in 774 SCA patients (OR = 1.7, P = 3.9 × 10–5). Thus, erythroid gene transcription responds to unique conditions within SCA erythroblasts and these changes potentially correspond to vaso-occlusive manifestations.

Abstract Microplastics (

Acute myeloid leukemia (AML) is a severe and fatal form of leukemia that is prevalent in the older population. In this longitudinal retrospective study, we investigated the epidemiology and survival rates of patients diagnosed with de novo acute myeloid leukemia in South Korea from Jan 1, 2011, to Aug 31, 2020. We used real-world data from the Health Insurance Review and Assessment Service database. We observed an increase in the number of acute myeloid leukemia cases, with age-specific incidence rates escalating in older patients. In contrast a long-term decrease from 1.94 to 1.77 per 100,000 individuals was found in the age-standardized incidence rates. Meanwhile, age-standardized prevalence rates ascended from 8.93 to 9.67 per 100,000 individuals, with a remarkable increase in the age-specific prevalence rate for those aged 80 years and above. Survival rates were notably better in younger or treated patients, and in those who underwent Hematopoietic stem cell transplantation. The time of diagnosis did not affect the survival of patients younger than 65 years. However, the most recent survival rates were significantly lower for patients 65 or older, as shown in the unadjusted Cox survival analysis. After adjustments in the analysis, it was found that the overall survival rates of the most recently diagnosed group improved significantly compared with those diagnosed earlier, with a hazard ratio of 0.90 (95% confidence interval, 0.84-0.97). This improvement may potentially be influenced by the enhanced treatment alternatives available for newly diagnosed older patients aged 65 years or older. In conclusion, aging appears to fuel an increase in the number of acute myeloid leukemia cases and mortality. Further studies are warranted to understand the impact of aging on acute myeloid leukemia treatment outcomes and devise efficacious care strategies for older patients.

Verifying habitats, including the foraging and nesting areas for sea turtles, enables an understanding of their spatial ecology and successful planning of their conservation and management strategies. Recently, the observation frequency and bycatch of loggerhead (Caretta caretta) and green (Chelonia mydas) turtles have increased in the northern limit of their distribution range, in the northern part of the East China Sea and East (Japan) Sea. We conducted satellite tracking to investigate the habitat use of seven loggerhead and eight green turtles from June 2016 to August 2022 in this area, where little is known about their spatial ecology. We applied a 50 percent volume contour method to determine their main foraging areas and analyzed 6 environmental variables to characterize their habitats. Loggerhead turtles mainly stayed in and used the East China Sea as a foraging area during the tracking period, while two individuals among them also used the East Sea as a seasonal foraging area. Most green turtles also used the East China Sea as a foraging area, near South Korea and Japan, with one individual among them using the lower area of the East Sea as a seasonal foraging area. Notably, one green turtle traveled to Hainan Island in the South China Sea, a historical nesting area. Our results showed that the two sea turtle species included the East Sea as a seasonal foraging area, possibly owing to the abundance of food sources available, despite its relatively lower sea temperature. Considering that loggerhead and green sea turtles were observed using the northern part of the East China Sea and East Sea more frequently than previously known and that the sea temperature gradually increases due to climate change, conservation and management activities are required for sea turtles in these areas.

AbstractBackground & Aims Individuals with high blood pressure (BP) have varying risks of cardiovascular events due to other coexisting factors. We aimed to identify the predictors of long-term absence of coronary artery calcium (CAC) in individuals with high BP, which is an indicator of healthy arterial aging and can guide preventive strategies.Methods We analyzed data from participants with high BP (≥120/80 mm Hg) in the Multi-Ethnic Study of Atherosclerosis who had baseline CAC = 0 and underwent a second CAC scanning after 10 years. We used multivariable logistic regression to evaluate the association between various risk factors for atherosclerotic cardiovascular disease (ASCVD) and long-term CAC = 0. We also calculated the area under the receiver operating characteristic curve (AUC) to predict the phenotype of healthy arterial aging in this population.Results We included 830 participants (37.6% male, mean ± SD age of 59.4 ± 8.7 years). During follow-up, 46.5% of participants (n = 386) had CAC = 0, and they were younger and had fewer metabolic syndrome components. Adding ASCVD risk factors to the demographic model (age, sex, and ethnicity) moderately increased the predictive value for long-term CAC = 0 (AUC: demographic model + ASCVD risk factors vs. demographic model alone, 0.653 vs. 0.597, p

Objectives Measuring the quality of care is paramount to inform policies for healthcare services. Nevertheless, little is known about the quality of primary care and acute care provided in Korea. This study investigated trends in the quality of primary care and acute care. Methods Case-fatality rates and avoidable hospitalization rates were used as performance indicators to assess the quality of primary care and acute care. Admission data for the period 2008 to 2020 were extracted from the National Health Insurance Claims Database. Case-fatality rates and avoidable hospitalization rates were standardized by age and sex to adjust for patients’ characteristics over time, and significant changes in the rates were identified by joinpoint regression. Results The average annual percent change in age-/sex-standardized case-fatality rates for acute myocardial infarction was -2.3% (95% confidence interval, -4.6 to 0.0). For hemorrhagic and ischemic stroke, the age-/sex-standardized case-fatality rates were 21.8% and 5.9%, respectively in 2020; these rates decreased since 2008 (27.1 and 8.7%, respectively). The average annual percent change in age-/sex-standardized avoidable hospitalization rates ranged from -9.4% to -3.0%, with statistically significant changes between 2008 and 2020. In 2020, the avoidable hospitalization rates decreased considerably compared with the 2019 rate because of the coronavirus disease 2019 pandemic. Conclusions The avoidable hospitalization rates and case-fatality rates decreased overall during the past decade, but they were relatively high compared with other countries. Strengthening primary care is an essential requirement to improve patient health outcomes in the rapidly aging Korean population.

Abstract Background Exome sequencing (ES) is becoming more widely available in prenatal diagnosis. However, data on its clinical utility and integration into clinical management remain limited in practice. Herein, we report our experience implementing prenatal ES (pES) in a large cohort of fetuses with anomalies detected by ultrasonography using a hospital-based in-house multidisciplinary team (MDT) facilitated by a three-step genotype-driven followed by phenotype-driven analysis framework. Methods We performed pES in 1618 fetal cases with positive ultrasound findings but negative for karyotyping and chromosome microarray analysis between January 2014 and October 2021, including both retrospective (n=565) and prospective (n=1053) cohorts. The diagnostic efficiency and its correlation to organ systems involved, phenotypic spectrum, and the clinical impacts of pES results on pregnancy outcomes were analyzed. Results A genotype-driven followed by phenotype-driven three-step approach was carried out in all trio pES. Step 1, a genotype-driven analysis resulted in a diagnostic rate of 11.6% (187/1618). Step 2, a phenotype-driven comprehensive analysis yielded additional diagnostic findings for another 28 cases (1.7%; 28/1618). In the final step 3, data reanalyses based on new phenotypes and/or clinical requests found molecular diagnosis in 14 additional cases (0.9%; 14/1618). Altogether, 229 fetal cases (14.2%) received a molecular diagnosis, with a higher positive rate in the retrospective than the prospective cohort (17.3% vs. 12.4%, p

Since the 2000s, sporadic outbreaks of whooping cough have been reported in advanced countries, where the acellular pertussis vaccination rate is relatively high, and in developing countries. Small-scale whooping cough has also continued in many countries, due in part to the waning of immune protection after childhood vaccination, necessitating the development of an improved pertussis vaccine and vaccination program. Currently, two different production platforms are being actively pursued in Korea; one is based on the aP (acellular pertussis) vaccine purified from B. pertussis containing pertussis toxoid (PT), filamentous hemagglutin (FHA) and pertactin (PRN), and the other is based on the recombinant aP (raP), containing genetically detoxified pertussis toxin ADP-ribosyltransferase subunit 1 (PtxS1), FHA, and PRN domain, expressed and purified from recombinant E. coli. aP components were further combined with diphtheria and tetanus vaccine components as a prototype DTaP vaccine by GC Pharma (GC DTaP vaccine). We evaluated and compared the immunogenicity and the protective efficacy of aP and raP vaccines in an experimental murine challenge model: humoral immunity in serum, IgA secretion in nasal lavage, bacterial clearance after challenge, PTx (pertussis toxin) CHO cell neutralization titer, cytokine secretion in spleen single cell, and tissue resident memory CD4+ T cell (CD4+ TRM cell) in lung tissues. In humoral immunogenicity, GC DTaP vaccines showed high titers for PT and PRN and showed similar patterns in nasal lavage and IL-5 cytokine secretions. The GC DTaP vaccine and the control vaccine showed equivalent results in bacterial clearance after challenge, PTx CHO cell neutralization assay, and CD4+ TRM cell. In contrast, the recombinant raP vaccine exhibited strong antibody responses for FHA and PRN, albeit with low antibody level of PT and low titer in PTx CHO neutralization assay, as compared to control and GC DTaP vaccines. The raP vaccine provided a sterile lung bacterial clearance comparable to a commercial control vaccine after the experimental challenge in murine model. Moreover, raP exhibited a strong cytokine response and CD4+ TRM cell in lung tissue, comparable or superior to the experimental and commercial DTaP vaccinated groups. Contingent on improving the biophysical stability and humoral response to PT, the raP vaccine warrants further development as an effective alternative to aP vaccines for the control of a pertussis outbreak.

Arecoline is the primary active carcinogen found in areca nut and has been implicated in the pathogenesis of oral squamous cell carcinoma (OSCC) and oral submucous fibrosis (OSF). For this study, we conducted a stepwise review process by combining iterative scoping reviews with a post hoc search, with the aim of identifying the specific mechanisms by which arecoline initiates and promotes oral carcinogenesis. Our initial search allowed us to define the current trends and patterns in the pathophysiology of arecoline-induced OSF and OSCC, which include the induction of cell proliferation, facilitation of invasion, adhesion, and migration, increased collagen deposition and fibrosis, imbalance in immune and inflammatory mechanisms, and genotoxicity. Key molecular pathways comprise the activation of NOTCH1, MYC, PRDX2, WNT, CYR61, EGFR/Pl3K, DDR1 signaling, and cytokine upregulation. Despite providing a comprehensive overview of potential pathogenic mechanisms of OSF, the involvement of molecules functioning as areca alkaloid receptors, namely, the muscarinic and nicotinic acetylcholine receptors (AChRs), was not elucidated with this approach. Accordingly, our search strategy was refined to reflect these evidence gaps. The results of the second round of reviews with the post hoc search highlighted that arecoline binds preferentially to muscarinic AChRs, which have been implicated in cancer. Consistently, AChRs activate the signaling pathways that partially overlap with those described in the context of arecoline-induced carcinogenesis. In summary, we used a theory-driven interpretive review methodology to inform, extend, and supplement the conventional systematic literature assessment workflow. On the one hand, the results of this critical interpretive synthesis highlighted the prevailing trends and enabled the consolidation of data pertaining to the molecular mechanisms involved in arecoline-induced carcinogenesis, and, on the other, brought up knowledge gaps related to the role of the local cholinergic axis in oral carcinogenesis, thus suggesting areas for further investigation.

Piperine is a plant-derived promising piperamide candidate isolated from the black pepper (Piper nigrum L.). In the last few years, this natural botanical product and its derivatives have aroused much attention for their comprehensive biological activities, including not only medical but also agricultural bioactivities. In order to achieve sustainable development and improve survival conditions, looking for environmentally friendly pesticides with low toxicity and residue is an extremely urgent challenge. Fortunately, plant-derived pesticides are rising like a shining star, guiding us in the direction of development in pesticidal research. In the present review, the recent progress in the biological activities, mechanisms of action, and structural modifications of piperine and its derivatives from 2020 to 2023 are summarized. The structure-activity relationships were analyzed in order to pave the way for future development and utilization of piperine and its derivatives as potent drugs and pesticides for improving the local economic development.

Abstract Age-related macular degeneration (AMD) is a major cause of vision loss in the elderly population. Anti-vascular endothelial growth factor (VEGF) antibody therapy is applicable to neovascularisation of AMD; however, the prevention of fibrosis after anti-VEGF monotherapy is an unmet medical need. Subretinal fibrosis causes vision loss in neovascular age-related macular degeneration (nAMD) even with anti-VEGF therapy. We report the anti-fibrotic and anti-neovascularisation effects of alpinumisoflavone (AIF), an isoflavonoid derived from unripe Maclura tricuspidata fruit, in in vitro and in vivo models. For in vitro study, we treated H2O2 or THP-1 conditioned media (TCM) following activation with phorbol 12-myristate 13-acetate (PMA) and lipopolysaccharide (LPS) in a human retinal pigment epithelial cell line (ARPE-19). Choroidal neovascularisation (CNV) was induced by laser photocoagulation in mice, immediately followed by intravitreal administration of 25 μg AIF. CNV area and fibrosis were measured 7 days after laser photocoagulation. AIF showed anti-fibrosis and anti-neovascularisation effects in both the models. The laser induced CNV area was reduced upon AIF administration in nAMD mouse model. Additionally, AIF decreased the levels of the cleaved form of crystallin alpha B (CRYAB), a chaperone associated with VEGF stabilisation and fibrosis. Our results demonstrate a novel therapeutic application of AIF against neovascularisation and fibrosis in nAMD.

Abstract Despite decades of research on suicide risk factors in young people, there has been no significant improvement in our understanding of this phenomenon. This study adopts a positive deviance approach to identify individuals with suicide resilience and to describe their associated psychological and sociodemographic profiles. Australian young adults aged 18–25 years with suicidal thoughts (N = 557) completed an online survey covering sociodemographic, mental health status, emotion regulatory and suicide-related domains. Latent class analysis was used to identify the individuals with suicide resilience. The predictors of suicide resilience were assessed using logistic regression models. The results suggested that one in ten (n = 55) met the criteria for suicide resilience. Factors that had a significant association with suicide resilience included greater cognitive flexibility, greater self-efficacy in expressing positive affect, reduced use of digital technology and less self-harm and substance use as a response to emotional distress. This study identified the factors that may protect young adults with suicidal thoughts from progressing to suicide attempts. Suicide prevention programs might be optimised by shifting from a deficit-based to a strength-based approach through promoting cognitive flexibility, self-efficacy and reducing maladaptive coping.

Introduction Meta-analytical evidence confirms a range of interventions, including mindfulness, physical activity and sleep hygiene, can reduce psychological distress in university students. However, it is unclear which intervention is most effective. Artificial intelligence (AI)-driven adaptive trials may be an efficient method to determine what works best and for whom. The primary purpose of the study is to rank the effectiveness of mindfulness, physical activity, sleep hygiene and an active control on reducing distress, using a multiarm contextual bandit-based AI-adaptive trial method. Furthermore, the study will explore which interventions have the largest effect for students with different levels of baseline distress severity.Methods and analysis The Vibe Up study is a pragmatically oriented, decentralised AI-adaptive group sequential randomised controlled trial comparing the effectiveness of one of three brief, 2-week digital self-guided interventions (mindfulness, physical activity or sleep hygiene) or active control (ecological momentary assessment) in reducing self-reported psychological distress in Australian university students. The adaptive trial methodology involves up to 12 sequential mini-trials that allow for the optimisation of allocation ratios. The primary outcome is change in psychological distress (Depression, Anxiety and Stress Scale, 21-item version, DASS-21 total score) from preintervention to postintervention. Secondary outcomes include change in physical activity, sleep quality and mindfulness from preintervention to postintervention. Planned contrasts will compare the four groups (ie, the three intervention and control) using self-reported psychological distress at prespecified time points for interim analyses. The study aims to determine the best performing intervention, as well as ranking of other interventions.Ethics and dissemination Ethical approval was sought and obtained from the UNSW Sydney Human Research Ethics Committee (HREC A, HC200466). A trial protocol adhering to the requirements of the Guideline for Good Clinical Practice was prepared for and approved by the Sponsor, UNSW Sydney (Protocol number: HC200466_CTP).Trial registration number ACTRN12621001223820.

BackgroundLGBTQ+ community's higher susceptibility to worse mental health outcomes and more help-seeking barriers compared to the cis-heterosexual population. Despite the LGBTQ+ population facing higher mental health risks, there has been a dearth of research focusing on developing tailored interventions targeting them. This study aimed to assess the effectiveness of a digital multicomponent intervention in promoting help-seeking for mental health issues in LGBTQ+ young adults.Methods and findingsWe recruited LGBTQ+ young adults aged between 18 and 29 who scored moderate or above on at least 1 dimension of the Depression Anxiety Stress Scale 21 and did not have help-seeking experiences in the past 12 months. Participants (n = 144) were stratified by gender assigned at birth (male/female) and randomly allocated (1:1 ratio) to the intervention or active control parallel condition by generating a random number table, so they were blinded to the intervention condition. All participants received online psychoeducational videos, online facilitator-led group discussions, and electronic brochures in December 2021 and January 2022, with the final follow-up in April 2022. The contents of the video, discussion, and brochure are help-seeking for the intervention group and general mental health knowledge for the control group. The primary outcomes were help-seeking intentions for emotional problems and suicidal ideation and attitudes toward seeking help from mental health professionals at the 1-month follow-up. The analysis was performed by including all participants based on their randomized group regardless of adherence to the protocol. A linear mixed model (LMM) was used for analysis. All models were adjusted for baseline scores. Chinese Clinical Trial Registry: ChiCTR2100053248. A total of 137 (95.1%) participants completed a 3-month follow-up, and 4 participants from the intervention condition and 3 from the control condition did not complete the final survey. Compared with the control group (n = 72), a significant improvement was found in help-seeking intentions for suicidal ideation in the intervention group (n = 70) at post-discussion (mean difference = 0.22, 95% CI [0.09, 0.36], p = 0.005), 1-month (mean difference = 0.19, 95% CI [0.06, 0.33], p = 0.018), and 3-month follow-ups (mean difference = 0.25, 95% CI [0.11, 0.38], p = 0.001). There was also a significant improvement in the intervention condition on the help-seeking intention for emotional problems at 1-month (mean difference = 0.17, 95% CI [0.05, 0.28], p = 0.013) and 3-month follow-ups (mean difference = 0.16, 95% CI [0.04, 0.27], p = 0.022) compared with the control group. Participants' depression and anxiety literacy and help-seeking encouragement related knowledge in intervention conditions showed significant improvements. There were no significant improvements in actual help-seeking behaviors, self-stigma toward seeking professional assistance, depression, and anxiety symptoms. No adverse events or side effects were observed. However, the follow-up time point was limited to 3 months which might not be long enough for drastic mindset and behavioral changes in help-seeking to occur.ConclusionsThe current intervention was an effective approach in promoting help-seeking intentions, mental health literacy, and help-seeking encouragement-related knowledge. Its brief yet integrated intervention format could also be utilized in treating other imminent concerns confronted by LGBTQ+ young adults.Trial registrationChictr.org.cn, ChiCTR2100053248.

Abstract The SARS-CoV-2 Omicron variant shows substantial resistance to neutralization by infection- and vaccination-induced antibodies, highlighting the demands for research on the continuing discovery of broadly neutralizing antibodies (bnAbs). Here, we developed a panel of bnAbs against Omicron and other variants of concern (VOCs) elicited by vaccination of adenovirus-vectored COVID-19 vaccine (Ad5-nCoV). We also investigated the human longitudinal antibody responses following vaccination and demonstrated how the bnAbs evolved over time. A monoclonal antibody (mAb), named ZWD12, exhibited potent and broad neutralization against SARS-CoV-2 variants Alpha, Beta, Gamma, Kappa, Delta, and Omicron by blocking the spike protein binding to the angiotensin-converting enzyme 2 (ACE2) and provided complete protection in the challenged prophylactic and therapeutic K18-hACE2 transgenic mouse model. We defined the ZWD12 epitope by determining its structure in complex with the spike (S) protein via cryo-electron microscopy. This study affords the potential to develop broadly therapeutic mAb drugs and suggests that the RBD epitope bound by ZWD12 is a rational target for the design of a broad spectrum of vaccines.

BackgroundIdiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with chronic, progressive lung fibrosis with a poor prognosis. Recent studies have reported a high prevalence of obstructive sleep apnea (OSA) in IPF patients and an association with poor prognosis. This study aimed to evaluate the prevalence, risk factors, and clinical effects on mortality of OSA in patients with IPF.MethodsClinical data were retrospectively analyzed in 167 patients with IPF at Haeundae-Paik Hospital, Republic of Korea. A type 4 portable device was used to monitor OSA, and an apnea-hypopnea index of 5 events per sleep hour and above was diagnosed as OSA.ResultsThe mean follow-up period and age were 26.9 months and 71.4 years, respectively, with male predominance. OSA was confirmed in 108 patients (64.7%). Mild OSA was the most common (62.1%). Independent risk factors for OSA in the multivariate logistic regression analysis were age (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.02-1.13, p = 0.007), body weight (OR 1.05, 95% CI 1.02-1.09, p = 0.002), and risk based on the Berlin questionnaire (OR 2.76, 95% CI 1.12-6.80, p = 0.028). Shorter six-minute walk distance (6MWD) (hazard ratio [HR] 1.00, 95% CI: 1.00-1.00, p < 0.001), acute exacerbation (AE) (HR 13.83, 95% CI: 5.71-33.47, p < 0.001), and higher percentage of cumulative time with oxygen saturation below 90% in total sleep time (HR 1.08, 95% CI: 1.02-1.14, p = 0.007) were risk factors for mortality in IPF patients in the Cox regression analysis.ConclusionApproximately two-thirds of the IPF patients had OSA. Older age, higher body weight, and high risk based on the Berlin questionnaire were independent risk factors for OSA in IPF patients. Shorter 6MWD, experience of AE, and night hypoxemia during sleep were associated with a higher risk of mortality in patients with IPF.

Abstract Background Inhalation injury from smoke or chemical products and carbon monoxide poisoning are major causes of death in burn patients from fire accidents. Respiratory tract injuries from inhalation injury and carbon monoxide poisoning can lead to acute respiratory distress syndrome and cytokine storm syndrome. In the case of acute respiratory failure needing mechanical ventilation accompanied by cytokine storm, mortality is high and immediate adequate treatment at the emergency department is very important. Case presentation This report describes a case of acute respiratory distress syndrome and cytokine storm followed by carbon monoxide poisoning in a 34-year-old Korean male patient who was in a house fire, and was successfully treated by extracorporeal membrane oxygenation and direct hemoperfusion with polymyxin B-immobilized fiber column at emergency department. Conclusions To prevent mortality in acute respiratory distress syndrome with cytokine storm from inhalation injury and to promote a better prognosis, we suggest that early implication of extracorporeal membranous oxygenation along with direct hemoperfusion with polymyxin B-immobilized fiber column even at the emergency department should be considered.

Background Suicidal ideation is a major risk for a suicide attempt in younger people, such that reducing severity of ideation is an important target for suicide prevention. Smartphone applications present a new opportunity for managing ideation in young adults; however, confirmatory evidence for efficacy from randomized trials is lacking. The objective of this study was to assess whether a therapeutic smartphone application (“LifeBuoy”) was superior to an attention-matched control application at reducing the severity of suicidal ideation. Methods and findings In this 2-arm parallel, double-blind, randomized controlled trial, 455 young adults from Australia experiencing recent suicidal ideation and aged 18 to 25 years were randomly assigned in a 2:2 ratio to use a smartphone application for 6 weeks in May 2020, with the final follow-up in October 2020. The primary outcome was change in suicidal ideation symptom severity scores from baseline (T0) to postintervention (T1) and 3-month postintervention follow-up (T2), measured using the Suicidal Ideation Attributes Scale (SIDAS). Secondary outcomes were symptom changes in depression (Patient Health Questionnaire-9, PHQ-9), generalized anxiety (Generalized Anxiety Disorder-7, GAD-7), distress (Distress Questionnaire-5, DQ5), and well-being (Short Warwick–Edinburgh Mental Well-Being Scale, SWEMWBS). This trial was conducted online, using a targeted social media recruitment strategy. The intervention groups were provided with a self-guided smartphone application based on dialectical behavior therapy (DBT; “LifeBuoy”) to improve emotion regulation and distress tolerance. The control group were provided a smartphone application that looked like LifeBuoy (“LifeBuoy-C”), but delivered general (nontherapeutic) information on a range of health and lifestyle topics. Among 228 participants randomized to LifeBuoy, 110 did not complete the final survey; among 227 participants randomized to the control condition, 91 did not complete the final survey. All randomized participants were included in the intent-to-treat analysis for the primary and secondary outcomes. There was a significant time × condition effect for suicidal ideation scores in favor of LifeBuoy at T1 (p < 0.001, d = 0.45) and T2 (p = 0.007, d = 0.34). There were no superior intervention effects for LifeBuoy on any secondary mental health outcomes from baseline to T1 or T2 [p-values: 0.069 to 0.896]. No serious adverse events (suicide attempts requiring medical care) were reported. The main limitations of the study are the lack of sample size calculations supporting the study to be powered to detect changes in secondary outcomes and a high attrition rate at T2, which may lead efficacy to be overestimated. Conclusions LifeBuoy was associated with superior improvements in suicidal ideation severity, but not secondary mental health outcomes, compared to the control application, LifeBuoy-C. Digital therapeutics may need to be purposefully designed to target a specific health outcome to have efficacy. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12619001671156 In a randomized controlled trial, Michelle Torok, Jin Han, and colleagues study the effectiveness of the LifeBuoy therapeutic smartphone application for reducing suicidal ideation in young adults in Australia. Author summary Why was this study done? Young people are a priority group for suicide prevention efforts, accounting for around one-third of all suicides. Suicidal ideation confers a moderate risk for suicide attempt and death, making it a novel, modifiable target for suicide prevention. Young people are poor help seekers for suicidal thoughts and behaviors; however, their willingness to engage with technology for mental health support creates enormous potential for smartphone interventions to improve access to help in this group. We identified only 2 prior trials of smartphone applications for treating suicidal ideation in younger people, neither which was tested in general population, nonclinical samples. Randomized trials are needed to understand if self-guided digital therapeutics work, are safe, and should be made available to young people. What did the researchers do and find? We conducted a 2-arm parallel randomized controlled trial to examine the effects of a brief, self-guided smartphone intervention (LifeBuoy) designed to reduce the severity of suicidal ideation by teaching emotional regulation and distress tolerance skills compared to a nontherapeutic, attention-matched “sham” application. Participants had access to the application they were randomly assigned to for 6 weeks and then were assessed at the end of the intervention period and 3 month later to determine if their baseline suicidal ideation scores had reduced. Young adults who received the LifeBuoy application showed greater reductions in suicidal ideation both immediately and at 3 months after the intervention compared to those who had received the control application. At postintervention, approximately 3 out of 4 young adults in the LifeBuoy group no longer had suicidal ideation score in a threshold that placed them at high risk of suicide attempt, compared to 1 out of 2 in the control group. Depression, anxiety, distress, and well-being symptoms improved from baseline to postintervention for young adults in both groups, but the LifeBuoy application did not lead to superior improvements above and beyond those observed in the control group. The LifeBuoy application appeared to be safe, with no young adults in the intervention group reporting suicide attempts at final follow up. What do these findings mean? Despite its brief nature and self-guided format, this dialectical behavior therapy (DBT) smartphone application can be used to modestly reduce the severity of suicidal ideation in young adults, making it a potentially useful therapeutic support for young people who might not otherwise be able or willing to access face-to-face treatment. Smartphone applications appear to work best when designed to target a specific health problem, with the current study supporting findings from other studies that digital therapeutics appear to be less effective for secondary health problems. Further investigation is needed to understand the full clinical meaningfulness of the findings, including which young people might benefit the most from this intervention.

Introduction Youth suicidal ideation and behaviour is concerning due to its widespread prevalence, morbidity and potentially fatal consequences. Digital mental health interventions have been found to improve access to low-cost and high-quality support for a range of mental health issues, yet there are few digital interventions available for suicide prevention in young people. In addition, no studies have examined how digital engagement strategies may impact the engagement and efficacy of digital interventions in suicide prevention. The current protocol describes a three-arm parallel randomised controlled trial. A therapeutic smartphone application (‘LifeBuoy’; intervention condition) will be tested against a condition that consists of the LifeBuoy application plus access to a digital engagement strategy (‘LifeBuoy+engagement’; intervention condition) to determine whether the addition of the digital strategy improves app engagement metrics. To establish the efficacy of the LifeBuoy application, both of these intervention conditions will be tested against an attention-matched control condition (a placebo app).Methods and analysis 669 young Australians aged 17–24 years who have experienced suicidal ideation in the past 30 days will be recruited by Facebook advertisement. The primary outcomes will be suicidal ideation severity and level of app engagement. Primary analyses will use an intention-to-treat approach and compare changes from baseline to 30-day, 60-day and 120-day follow-up time points relative to the control group using mixed-effect modelling. A subset of participants in the intervention groups will be interviewed on their experience with the app and engagement strategy. Qualitative data will be analysed using an inductive approach, independent of a theoretical confirmative method to identify the group themes.Ethics and dissemination The study has been approved by the University of New South Wales Human Research Ethics Committee (HC210400). The results of the trial will be disseminated via peer-reviewed publications in scientific journals and conferences.Trial registration number ACTRN12621001247864.

Objectives Deep neck infections (DNIs) can cause life-threatening complications, and prompt diagnosis and management are necessary. Kawasaki disease (KD) may be accompanied by deep neck inflammation; making it difficult to distinguish from DNIs. This study was performed to evaluate clinical features and outcomes of children with parapharyngeal and retropharyngeal inflammation. Methods Medical records of the children diagnosed with parapharyngeal and retropharyngeal cellulitis or abscess using cervical computed tomography (CT) between 2013 and 2017 were retrospectively reviewed. Results A total of 47 children were diagnosed with parapharyngeal and retropharyngeal inflammation. Eleven (23.4%) of them were eventually diagnosed with KD, and 36 (76.6%) were diagnosed with DNIs. There were no significantly different clinical and laboratory characteristics on admission between children diagnosed with KD and DNIs; however, significantly more children with KD were febrile for ≥3 days after admission compared to those with DNIs (P=0.009). Deep neck abscesses on CT were observed in 16 children with DNIs (44.4%) and in no child with KD (P=0.009). Among the 36 children with DNIs, 30 (83.3%) were cured with antibiotic therapy only. Conclusion A quarter of children presenting with deep neck inflammation were diagnosed with KD. KD should be considered in children showing deep neck inflammation unresponsive to empirical antibiotic therapy after 3 days, especially in those presenting with deep neck cellulitis rather than deep neck abscess.

Background Errors in counting spinal segments are common during interventional procedures when there are transitional vertebrae. In this study, we investigated the prevalence of the transitional vertebrae including thoracolumbar transitional vertebra (TLTV) and lumbosacral transitional vertebrae (LSTV). The relationship between the existence of TLTV and abnormal rib count or the existence of LSTV were also evaluated. Methods The vertebral levels were counted craniocaudally, starting from C1, based on the assumption of 7 cervical, 12 thoracic, and 5 lumbar vertebrae, using whole spine spiral three-dimensional computed tomographic images. The 20th and 25th vertebrae were defined as L1 and S1, respectively. Results In total, 150 patients had TLTV, with a prevalence of 11.2% (150/1,340). LSTV was observed in 111 of 1,340 cases (8.3%). Sacralization was observed in 68 of 1,340 cases (5.1%) and lumbarization in 43 of 1,340 cases (3.2%). There was a significant relationship between the existence of TLTV and the abnormal rib count (odds ratio [OR]: 117.26, 95% confidence interval [95% CI]: 60.77–226.27; P < 0.001) and LSTV (OR: 7.38, 95% CI: 3.99–13.63; P < 0.001). Conclusions Our study results suggest that patients with TLTV are more likely to have an abnormal rib count or LSTV. If a TLTV or LSTV is seen on the fluoroscopic image, a whole spine image is necessary to permit accurate numbering of the lumbar vertebra.

The iliopsoas plane (IP) is a fascial plane deep to the iliopsoas complex and is the target of several novel ultrasound-guided analgesic interventions for hip. Currently, limited information is known about its parameters. From the pelvic magnetic resonance (MR) images of an adult Eastern Asian population (n = 49), the IP width, depth, and needle-beam angle in the axial plane immediately caudal to the level of indirect tendon of rectus femoris (RF) were found to be 10.7 ± 1.6 mm, 48.5 ± 15.5 mm, and 84.2 ± 8.2 degrees, respectively. There was a statistically significant difference in the age categories for IP width, and older patients seemed to have wider IP. Our data may provide applications for the technical modification of ultrasound-guided iliopsoas plane block (IPB) in acute hip pain management and the future development of ultrasound-guided single-needle-entry radiofrequency neuroablation in chronic hip pain management.

Cancer: How a plant metabolite analog suppresses tumor growth A synthetic analog of a chemical found in fruit suppresses tumor growth by targeting an RNA-binding protein (hnRNPA2B1) and preventing the production of a pro-cancer regulatory factor. Nak-Kyun Soung from the Korea Research Institute of Bioscience and Biotechnology, Cheongju, South Korea, and coworkers built on their previous discovery that a compound derived from a medicinal plant metabolite can suppress the activity of hypoxia-inducible factor-1α (HIF-1α). This protein, which is involved in many aspects of cancer biology, is activated in the low-oxygen microenvironments found inside tumors. The researchers show that the compound binds to a protein that helps with the conversion of HIF-1α–encoding RNA transcripts into HIF-1α proteins. Liver cancer cells treated with the compound grew slowly and produced less HIF-1α under both normal and low-oxygen culture conditions, highlighting the potential of this anti-cancer strategy.

Fuzzy C-means clustering algorithm is one of the typical clustering algorithms in data mining applications. However, due to the sensitive information in the dataset, there is a risk of user privacy being leaked during the clustering process. The fuzzy C-means clustering of differential privacy protection can protect the user's individual privacy while mining data rules, however, the decline in availability caused by data disturbances is a common problem of these algorithms. Aiming at the problem that the algorithm accuracy is reduced by randomly initializing the membership matrix of fuzzy C-means, in this paper, the maximum distance method is firstly used to determine the initial center point. Then, the gaussian value of the cluster center point is used to calculate the privacy budget allocation ratio. Additionally, Laplace noise is added to complete differential privacy protection. The experimental results demonstrate that the clustering accuracy and effectiveness of the proposed algorithm are higher than baselines under the same privacy protection intensity.

Introduction Delirium is commonly missed in older adults presenting to the emergency department (ED). Although current recommendations for active screening of delirium in the ED, this might not be feasible or practical. Identifying patients at high risk for prevalent and incident delirium in the ED will help to improve the screening process and to build interventions. There is currently scattered synthesis of evidence on risk factors associated with delirium in the ED. To address this gap, we are conducting a systematic review to describe the risk factors (patient vulnerability factors and precipitating factors) for delirium in the ED.Methods and analysis A literature search was performed from inception to March 2020 in Ovid EBM Reviews, Ovid EMBASE, Ovid MEDLINE, Scopus and Web of Science. We will include original research studies that report a quantitative relationship between at least one risk factor and delirium in the ED setting. Two investigators will use eligibility criteria from this protocol to independently screen titles and abstracts, and select studies based on full-text review of potentially eligible studies. After arriving at a final set of included studies, two investigators will extract data using a standardised data collection form. If appropriate, data regarding each risk factor will be pooled through a random-effect meta-analysis. The Grading of Recommendations Assessment, Development and Evaluation approach will be used to evaluate the overall quality of evidence.Ethics and dissemination To our knowledge, this will be the first systematic review evaluating risk factors for prevalent and incident delirium specifically related to the ED setting. Results of this study will aid in the identification of older adults at risk for delirium in the ED. We aim to publish the results of this systematic review in a peer-reviewed journal with good visibility for the fields of emergency medicine and geriatrics.PROSPERO registration numberCDR42020175261

The objective of this study was to evaluate predicting factors for supraphysiologic serum estradiol elevation during controlled ovarian stimulation (COS) with administration of letrozole and gonadotropins in patients with estrogen-dependent cancer. Use of aromatase inhibitors is recommended to prevent the potential effects of elevated serum estradiol levels and recurrence of tumor in patients with estrogen-dependent cancers during COS. Although previous studies reported that letrozole have shown an effective lowering of peak estrogen levels, a part of patients shows supraphysiologic levels of estrogen associated with ovarian stimulation despite the administration of letrozole. From January 2009 to December 2019, patients with estrogen-dependent cancer who underwent COS with antagonist protocol using a letrozole (5 mg/ day) to keep estrogen levels low were included in this study. Early monitoring serum estradiol was measured in all patients on the 4-6th day of stimulation. Subjects were classified into two groups according to the serum estradiol level on hCG triggering day, physiologic estradiol group (≤400 pg/mL) and supraphysiologic estradiol group (>400 pg/mL). A total of 96 COS cycles were retrospectively analyzed. Supraphysiologic level of serum estradiol was found in 21.9% of the patients. Mean age, AMH, duration of stimulation, total dose of gonadotropins administered were not different between the two groups. However, early monitoring serum estradiol level was significantly higher in the supraphysiologic estradiol group (67.1±47.9 vs. 115.6±78.1, p = 0.001) and was associated with the occurrence of supraphysiologic elevation of serum estradiol on hCG triggering day. Patients with early monitoring serum estradiol ≥84.5 pg/mL had an odds ratio of 5.376 [95% CI, 1.613-17.913] for supraphysiologic elevation of serum estradiol compared to those with early monitoring serum estradiol below 84.5 pg/mL. In conclusion, early monitoring serum estradiol is an independent predicting factor for supraphysiologic level of serum estradiol on hCG triggering day in the COS cycles using letrozole and gonadotropins.

Shark meat is consumed as a food source worldwide, especially in Asian countries. However, since sharks are apex predators in the ocean food chain, they are prone to bioaccumulation of heavy metals. More than 100 million sharks are caught annually for human consumption, and the safety of shark meat cannot be overemphasized. Here, we examined heavy metal concentration in the muscle tissue of 6 shark species including 3 migratory species (Carcharhinus brachyurus, Carcharhinus obscurus, and Isurus oxyrinchus) and 3 local species (Triakis scyllium, Mustelus manazo, and Cephaloscyllium umbratile) from fish markets in Jeju Island, Republic of Korea. The concentrations of 11 heavy metals (Cr, Fe, Cu, Zn, As, Se, Cd, Sn, Sb, Pb, and Hg) and MeHg were analyzed. The result showed that the average concentrations of all metals, except for that of As, were below the regulatory maximum limits of many organizations, including the Codex standard. Hg and MeHg were significantly correlated with body length, body weight, and age, and the concentration of Hg was expected to exceed the limit in C. brachyurus with a body length or weight of over 130 cm or 25 kg, respectively. Our results indicate that shark meat can expose consumers to a high level of As and that copper sharks bigger than the predicted size should be avoided for excessive Hg. Considering these findings, a detailed guideline on consumption of meat of different shark species should be suggested based on further investigation.

Background: Polypharmacy and potentially inappropriate medications (PIMs) are prominent prescribing issues in elderly patients. This study was to investigate the different prevalence of PIM use in elderly inpatients between 65-79 years of age and 80 years or older, who were discharged from Geriatric Department in West China Hospital. Methods: A large-scale cohort of 1796 inpatients aged 65 years or over was recruited. Respectively, 618 patients were 65-79 years and 1178 patients were 80 years or older. Updated 2012 Beers Criteria by the American Geriatric Society was applied to assess the use of PIM among the investigated samples. Results: A review of the prescribed medications identified 686 patients aged 80 years or older consumed at least one PIM giving a rate of 58.2%. Conversely, 268 (43.4%) patients aged 65-79 years consumed at least one PIM (χ2 = 40.18, P < 0.001). Patients aged 80 years or older had higher hospitalization expenses, length of stay, co-morbidities, medical prescription, and mortality than patients aged 65-79 years (all with P < 0.001). Patients aged 80 years or older were prescribed with more benzodiazepines, drugs with strong anticholinergic properties, megestrol, antipsychotics, theophylline, and aspirin. In multiple regression analysis, PIM use was significantly associated with female gender, age, number of diagnostic disease, and number of prescribed medication. Conclusions: The finding from this study revealed that inpatients aged 80 years or older encountered more PIM use than those aged 65-79 years. Anticholinergic properties, megestrol, antipsychotics, theophylline, and aspirin are medications that often prescribed to inpatients aged 80 years or older. Doctors should carefully choose drugs for the elderly, especially the elderly aged 80 years or older.

The possible relationship between periodontal disease resulting from the infection of gingival tissue by the Gram-negative bacterium Porphyromonas gingivalis (P. gingivalis) and the development of neuroinflammation remains under investigation. Recently, P. gingivalis lipopolysaccharide (LPS) was reported in the human brain, thus suggesting it might activate brain microglia, a cell type participating in neuroinflammation. We tested the hypothesis of whether in vitro exposure to ultrapure P. gingivalis LPS may result in classical and alternative activation phenotypes of rat microglia, with the concomitant release of cytokines and chemokines, as well as superoxide anion (O2−), thromboxane B2 (TXB2), and matrix metalloprotease-9 (MMP-9). After an 18-h exposure of microglia to P. gingivalis LPS, the concentration-dependent responses were the following: 0.1–100 ng/mL P. gingivalis LPS increased O2− generation, with reduced inflammatory mediator generation; 1000–10,000 ng/mL P. gingivalis LPS generated MMP-9, macrophage inflammatory protein 1α (MIP-1α/CCL3), macrophage inflammatory protein-2 (MIP-2/CXCL2) release and significant O2− generation; 100,000 ng/mL P. gingivalis LPS sustained O2− production, maintained MMP-9, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) release, and triggered elevated levels of MIP-1α/CCL3, MIP-2/CXCL2, and cytokine-induced neutrophil chemoattractant 1 (CINC-1/CXCL-1), with a very low release of lactic dehydrogenase (LDH). Although P. gingivalis LPS was less potent than Escherichia coli (E. coli) LPS in stimulating TXB2, MMP-9, IL-6 and interleukin 10 (IL-10) generation, we observed that it appeared more efficacious in enhancing the release of O2−, TNF-α, MIP-1α/CCL3, MIP-2/CXCL2 and CINC-1/CXCL-1. Our results provide support to our research hypothesis because an 18-h in vitro stimulation with ultrapure P. gingivalis LPS resulted in the classical and alternative activation of rat brain microglia and the concomitant release of cytokines and chemokines.

Vibrio coralliilyticus is known as a coral pathogen that also infects marine bivalve larvae worldwide. It is considered to be one of the major constraints in artificial marine bivalve seed production as it causes mortality. In this study, we first isolated and characterized a high virulent of V. coralliilyticus designated as SNUTY-1 that was the cause of Pacific oyster larvae mortality in Korea. In the pathogenicity test, exposure to 2.14 × 105 CFU/mL for 24 h caused mortality to 88.65 ± 2.4% of the tested healthy Pacific oyster larvae. SNUTY-1 showed anti-microbial resistance to β-lactams, such as penicillins, cephalosporins, and carbapenems. We sequenced and assembled the complete genome of SNUTY-1 (5,842,676 bp), consisting of two chromosomes (Chr I and Chr II) and two plasmids (pSNUTY1 and pSNUTY2). The COG functional analysis confirmed that Chr I had more genes associated with basic cellular functions in comparison to Chr II. The results of the phylogenetic trees based on OrthoANI values indicated that the SNUTY-1 was closely related to V. coralliilyticus strains. SNUTY-1 had a unique plasmid (pSNUTY2), which could mean that the Korean isolate is different from other sequenced V. coralliilyticus strains from different geographical origins. Toxic proteins such as cytolysin/hemolysin and extracellular metalloprotease genes were encoded on Chr I and Chr II of SNUTY-1. These data facilitate the control of V. coralliilyticus infections in aquaculture by providing valuable insights into the biodiversity of this organism and valuable information for the study of virulence factors.

Three-dimensional (3D) computational aortic models have been established to reproduce aortic diseases such as aortic aneurysm and dissection; however, no such models have been developed to study diabetes mellitus (DM). To characterize biomechanical properties of the human aorta with DM, reconstructed aortic CT images were converted into DICOM format, and imported into the 3D segmentation using Mimics software. This resulted in a 3D reconstruction of the complete aorta, including three branches. We applied a pulsatile blood pressure waveform for the ascending aorta to provide a biomimetic environment using COMSOL Multiphysics software. Hemodynamics were compared between the control and DM models. We observed that mean blood flow velocity, aortic pressure, and von Mises stress values were lower in the DM model than in the control model. Furthermore, the range of aortic movement was lower in the DM model than in the control model, suggesting that the DM aortic wall is more susceptible to rupture. When comparing biomechanical properties in discrete regions of the aorta, all values were higher in the ascending aorta for both control and DM models, corresponding to the location of most aortic lesions. We have developed a compute based that integrates advanced image processing strategies and computational techniques based on finite element method to perform hemodynamics analysis based on CT images. Our study of image-based CFD analysis hopes to provide a better understanding of the relationship between aortic hemodynamic and developing pathophysiology of aortic diseases.